The work proposed represents continuation and extension of a systematic, comprehensive study of the macromolecular composition of articular cartilage proteoglycans (PGs) and the organization of PGs in cartilage matrix. In particular, changes relating to aging and to osteoarthritis (OA) are being examined. Abnormalities in PG aggregation have already been demonstrated and emphasis will now be directed toward elucidation of the basis for such abnormalities. Is there a defect in cartilage hyaluronic acid (HA), which plays a central role in aggregation of cartilage PGs? Are the PGs themselves abnormal and therefore unable to interact with HA? What is the molecular defect in the PGs or HA, and its pathogenesis? How does the aggregation defect observed in OA relate to aging? Studies of experimentally-induced canine OA will be performed to examine changes in the earliest stages of disease. The effect of the extracellular milieu on the function of chondrocytes from normal, aged and OA cartilage will be studied in culture. Specifically, changes in synthesis and degradation of PGs and HA which may result from alterations in extracellular collagen, HA and PGs will be explored. BIBLIOGRAPHIC REFERENCES: Palmoski, M.J. and Brandt, K.D.: Stimulation of glycosaminoglycan biosynthesis by amyloid fibrils. Biochem. J. 148:145-147, 1975. Brandt, K.D. and Palmoski, M.: Ground substance organization in osteoarthritis (OA), a disorder of proteoglycan aggregation. Arthritis Rheum. 18:389, 1975.